According to the report of 1998 on “Research on Increasing the Accuracy and the Utilization of the Population-Based Cancer Registry”, supported by a Grant-in-Aid for Cancer Research from the Ministry of Health, Labour and Welfare, Japan, 33,676 cases of breast cancer are reported in one year, and the age-adjusted incidence rate was 52.2 cases per 100,000 persons, becoming the number one malignant neoplasm in women, and these figures have increased approximately three-fold since 1970. The number of breast cancer patients has been increasing year by year, and it is predicted to reach 48,000 cases, 56.9/10,000 persons by 2015. Because of breast cancer's relatively good prognosis, according to the 2001 report by Vital Statistics of Japan, Statistics and Information Department, Minister's Secretariat, Ministry of Health, Labour and Welfare, the mortality rate for breast cancer is fifth among cancer sites in female cancer patients, but from age 50 onward the mortality rate is high. The standardized death rate tends to be higher in urban areas, and a 1999 report by the Japan Cancer Society shows that the standardized death rate in the Tokyo Metropolis is 132.2%, compared to 73.5% in Kagoshima Prefecture. This increase in the number of breast cancer patients seems to be related to changes in our lifestyle in recent years, and example of the reasons include longer menstrual periods, postmenopausal hormone supplement therapy, and alcohol consumption.
Most breast cancer is invasive ductal carcinoma arising from duct epithelium. Appropriate surgical treatment and chemotherapy will bring the cancer into temporary remission, but metastasis often occurs from the earliest stages, and the cancer reappears after a number of years, then develops bone, liver, brain, and lung metastases (carcinomatous lymphangitis) and frequently leads to death. The 5-year survival rate is 90% in stage I cases in which the tumor is 2 cm or less and there is no lymph node metastasis. Whereas in stage III and IV cases with skin/chest wall infiltration and 10 or more of lymph node metastases or distant metastases, the 5-year survival rate is about 70%.
Lymph node metastasis is the most important prognosis factor that affects these survival rates. A systemic metastasis mechanism via lymph nodes is predicted in many types of breast cancer, and in recent years, breast cancer has been increasingly viewed as a systemic disease. There are few specific markers for diagnosing metastasis, and thus the diagnosis of metastasis is frequently made by diagnostic imaging using primarily ultrasound, or fine-needle aspiration cytology. Effective treatments include surgical excision as well as antihormonal therapy and preoperative chemotherapy, and at the current time, monoclonal antibody against HER2/neu (Herceptin) has been applied as a molecular target drug to cases having metastasis.
The average prognosis for breast cancer differs depending on the medical facility, and the 5-year survival rate is 80% or more. However, there is a very poor prognosis group with a 5-year survival rate of approximately 40%, and in particular, this group exhibits widespread (numerous) lymph node metastasis from earlier stages, regardless of the size of the tumor. This group is classified as invasive micropapillary carcinoma under the histological classifications of the World Health Organization, and inflammatory breast cancer is a representative example thereof. Some known factors for defining the degree of malignancy, the degree of local progress, and the metastasis of breast cancer include cell growth ability, estrogen receptor, progesterone receptor, and HER2 (Woelfe U. et al., Cancer Res., (2003) vol. 63, pp. 5679-5684; Jacquemier J. et al., Cancer Res., (2005) vol. 65, pp. 767-779; Lim S M. and Elenitoba-Johnson K S J., Lab Invest., (2004) vol. 84, pp. 1227-1244; Adam P J. et al., J. Biol. Chem., (2003) vol. 278, pp. 6482-6489; and Jessani N. et al., Proc. Natl. Acad. Sci. USA, (2002) vol. 99, pp. 10335-10340).
With regard to cancer metastasis, and particularly the metastasis of breast cancer, a method for comprehensively examining expression level of risk markers by using MUC1 and keratin19 in the bone marrow of breast cancer patients as risk markers and quantifying their level of mRNA expression has been developed (Japanese Laid-Open Patent Publication No. 2004-151003). However, at the current time, means or methods for easily detecting the malignancy of breast cancer is not yet sufficiently established.